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Fetus’s arthritis genes can affect the mother

If the fetus has high-risk genes for arthritis, its mother is more likely to develop it later

(Image: EDELMANN/SCIENCE PHOTO LIBRARY)

Unborn babies can sow the seeds for rheumatoid arthritis in their mothers – and the dads might be to blame.

Rheumatoid arthritis is an autoimmune disease, meaning the body’s immune system turns on itself. In this case, it causes painful, swollen joints. Women are three times as likely to develop the condition as men, and seem to be especially vulnerable soon after pregnancy.

A mother exchanges cells with the fetus while it is in the womb. “For most women, shortly after you give birth, the fetal cells clear up,” says Giovanna Cruz, an epidemiologist at the University of California at Berkeley. “But in a subset of women they actually persist for decades.” In these women, the fetal cells are effectively incorporated into their bodies, a process known as microchimerism.

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DNA swap

Women who develop autoimmune diseases seem to have a higher incidence of microchimerism than other women. Two small studies have shown that mothers who genetically have a low risk of developing arthritis but go on to develop the disease are more likely to show microchimerism. What’s more this stowaway DNA contained high-risk genes for rheumatoid arthritis. But these studies didn’t look directly at the genes of the father or the child.

In the largest study to date, Cruz and her colleagues analysed genes associated with arthritis in women with the condition and in family members. They did the same for healthy women who had given birth to at least one child, and unrelated men. In total, they looked at over 5000 individuals.

They found that regardless of the women’s own genetic risk, those with the disease were twice as likely to have given birth to children who had high-risk genes – most likely passed down from the father.

But how exactly this triggers arthritis remains a mystery. “We still don’t know what these microchimeral cells are doing”, says Cruz, who presented the study at the American Society for Human Genetics meeting in San Diego this week. She speculates that it could be either maternal immune cells reacting to the presence of the fetal cells that triggers the response – in a similar way to a transplant patient’s body rejecting a donor organ – or it could be the stowaway fetal immune cells themselves launching the attack.

Dad’s fault?

“It is exciting to see work that has the potential to significantly advance our understanding,” says Lee Nelson at the University of Washington in Seattle, who carried out some of the initial work on arthritis and microchimerism.

Chris Deighton, medical adviser to the British Society for Rheumatology notes the peak age for the disease is around 70 and that it also affects men, as well as women who have never been pregnant. “It may be that fetal microchimerism would only account for a small proportion of the aetiology of the disease”. However, he adds that anything that helps us understand this “astonishingly complicated” disease is worth pursuing.

Future analysis of Cruz’s data will look at the genetic influence of the dads – to see if the partners of affected women are more likely to have high-risk genes than the partners of controls or unrelated men. They also plan to investigate whether having babies with genes known to decrease the risk of rheumatoid arthritis has any mitigating effect on mothers who already have the condition.